This investigation concerns the elucidation of mechanisms involved in the pathogenesis of brain injury induced by malnutrition. Nutritional disturbances are associated with a number of nervous system disorders in humans, especially children. The processes by which nutritional disturbances lead to brain injury are unknown or incompletely understood. Our studies of nutritional encephalomalacia (NE), an experimental model of nutritional brain injury in which infarcts and edema occur chiefly in the cerebellum of chicks, show that vascular changes representing an incompletely defined, selective injury of the CNS microcirculation precede parenchymal infarction and edema. The injury appears to involve the lipid constituents of the CNS microcirculatory endothelium. We have developed a method for isolating a relatively pure infraction of microcirculatory vessels from 1-2 grams of cerebrum or cerebellum. The proposed studies involve the quantitative biochemical analysis of CNS microcirculatory fractions from normal chicks and chicks with CNS microcirculatory injuries including NE. Specific and non-specific endothelial lipid alterations associated with the evolution of NE will be identified and characterized. The study will establish new methods for identifying and investigating CNS microcirculatory injuries including those resulting from lead intoxication or radiation and provide information concerning the effect of tocopherol deficiency on the CNS.